In contrast to experimental models of epilepsy involving tissue damage, pharmacological agents, or electrical stimulation, the immunoneurological model provides a clearly defined target for studying molecular mechanisms because of the well-recognized molecular specificity inherent in antigen-antibody reactions. Recurrent seizure activity in the EEG of several weeks duration can be produced in rats (and rabbits) by injection into the sensorimotor cortex (or intraventricularly) of 10 microliters of antiserum to synaptic membranes. The antigens in these membranes against which the effective antibodies are directed have not yet been chemically identified, and this model therefore retains some uncertainty. However, we have recently found a simple, reproducible immunological system that will permit extensive development based on firm neurochemical criteria, namely, the use of antiserum against brain ganglioside. Seizure activity induced by antiganglioside serum, which differs in some respects from that induced by antiserum to synaptic membranes, is eliminated completely by absorbing the antiserum with small quantities of pure GM1 ganglioside. This represents an ideal control. We wish to explore these immunoneurological models in order to: a) More carefully characterize the nature and specificity of the antibodies, b) Establish a basis for quantification of the seizure response in terms of its time of onset, its intensity, and its duration, c) To determine whether the models exhibit a regional specificity for induction of seizures, d) To establish the anatomical locus of activity through immunohistochemical localization of specific antigenic sites, and e) To compare the effects of antibodies with other agents that are known to react with a GM1 receptor (such as cholera toxin) or can potentially react with such a structure (such as the lectins). Pure antiganglioside antibodies will be prepared and used to determine dose-response relationships and localization of antigenic sites. Antigens present in synaptic membranes will be isolated and identified. The mechanism of action of these agents will be further explored.